Methotrexate can cause embryo-fetal toxicity, including fetal death. Use in pJIA is contraindicated
in pregnancy. Consider the benefits and risks of XATMEP and risks to the fetus when prescribing
XATMEP to a pregnant patient with a neoplastic disease. Advise females and males of reproductive
potential to use effective contraception during and after treatment with XATMEP [see Contraindications
(4), Warnings and Precautions (5.9), Use in Specific Populations (8.1, 8.3)].

INDICATIONS

Xatmep is a folate analog metabolic inhibitor indicated for the:

treatment of pediatric patients with acute lymphoblastic leukemia (ALL) as part of a multi-phase, combination chemotherapy
maintenance regimen

management of pediatric patients with active polyarticular juvenile idiopathic arthritis (pJIA) who have had
an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including
full dose non-steroidal anti-inflammatory agents (NSAIDs).

ADDITIONAL IMPORTANT SAFETY INFORMATION

Contraindications:

Xatmep is contraindicated in pregnant patients with non-malignant disease and in patients with severe
hypersensitivity to methotrexate.

Secondary malignancies can occur at all dose levels. Lymphoproliferative disease has been reported with
low-dose oral methotrexate which regressed when methotrexate is withdrawn.

Methotrexate can cause embryo-fetal toxicity and fetal death when administered during pregnancy. Consider the
risks and benefits of Xatmep and risks to the fetus when prescribing to a pregnant patient with a neoplastic
disease. Effective contraception should be practiced by patients of reproductive potential while receiving Xatmep
therapy, and for 3 and 6 months afterwards for males and females, respectively. Xatmep is contraindicated in
non-neoplastic disease.

Effects on reproduction: Methotrexate can cause impairment of fertility, oligospermia, and menstrual dysfunction.
It is unknown if the infertility is reversible in affected patients.

Pulmonary function tests may be useful if methotrexate-induced lung disease is suspected, especially
if baseline measurements are available.

Risk of improper dosing: Once-weekly dosing is appropriate. Fatal toxicity has been reported with daily dosing.
An accurate milliliter measuring device should be used. Inform patients that a household teaspoon is not an
accurate measuring device and could lead to overdosage.

Other frequently reported reactions are malaise, fatigue, chills and fever, dizziness, and decreased resistance
to infection.

The approximate incidences of adverse reactions reported in pediatric patients with JIA treated with oral, weekly
doses of methotrexate (5 to 20 mg/m2/week or 0.1 to 0.65 mg/kg/week) were as follows (virtually all patients
were receiving concomitant nonsteroidal anti-inflammatory drugs, and some also were taking low doses of
corticosteroids): elevated liver function tests, 14%; gastrointestinal reactions (e.g., nausea, vomiting, diarrhea),
11%; stomatitis, 2%; leukopenia, 2%; headache, 1.2%; alopecia, 0.5%; dizziness, 0.2%; and rash, 0.2%. Although
there is experience with dosing up to 30 mg/m2/week in JIA, the published data for doses above 20 mg/m2/week
are too limited to provide reliable estimates of adverse reaction rates.

Drug Interactions:

Penicillins may reduce the clearance of methotrexate; increased serum concentrations of methotrexate
with concomitant hematologic and gastrointestinal toxicity have been observed with methotrexate. Monitor
patients accordingly.

Denver, October 26, 2016 — Silvergate Pharmaceuticals, Inc. (www.silvergatepharma.com), leader in the development and commercialization of innovative and safe medicines for children, today announced that Qbrelis™ (lisinopril) oral solution, the first and only FDA-approved lisinopril oral solution, is now available for ordering. Qbrelis™ is indicated for the treatment of hypertension (high blood pressure) in adult patients and pediatric patients 6 years of age and older, adjunct therapy forheart failure, and treatment of acute myocardial infarction (heart attack) in adults.1

Silvergate Pharmaceuticals, Inc. (www.silvergatepharma.com) leaders in the development and commercialization of innovative and safe medicines for children, recently announced that the United States Food and Drug Administration (FDA) approved XATMEP (methotrexate) Oral Solution, the first and only FDA-approved methotrexate oral solution. XATMEP is indicated for the treatment of acute lymphoblastic leukemia (ALL) and polyarticular juvenile idiopathic arthritis (pJIA) in pediatric patients.

“XATMEP is an exciting product in that it provides an FDA-approved, ready-to-use oral solution of methotrexate for children without the need for needles, crushing of tablets or compounding into a liquid formulation,” said Frank Segrave, President & CEO, Silvergate Pharmaceuticals, Inc. “As a company, we continue to focus on pediatric medications that are safe, effective, and readily available.”

XATMEP (methotrexate) Oral Solution, 2.5 mg/mL, is a ready-to-use product that requires no preparation, facilitating accuracy and ease of dispensing at the pharmacy. XATMEP is manufactured under CGMPs in accordance with FDA regulations. It eliminates the need for needles, crushing or splitting tablets or for compounding tablets into a liquid formulation. It requires refrigeration but may be stored at room temperature for 60 days after dispensing. XATMEP will be available soon. For additional information on how to obtain XATMEP, please call 1-855-379-0382.

About XATMEP
XATMEP (methotrexate) Oral Solution was developed, primarily, to meet the need for a ready-to-use, 2.5 mg/mL, methotrexate oral solution for the treatment of pediatric patients for the indications stated above. Prior to Xatmep, there was no FDA-approved, ready-to-use oral liquid formulation of methotrexate for use by pediatric patients requiring body surface area (BSA) dosing (mg/m2) or who have difficulty swallowing or cannot consume tablets, or those with needle-phobia. Silvergate Pharmaceuticals, Inc.’s XATMEP (methotrexate) Oral Solution resolves these unmet medical needs in pediatric patients.

Methotrexate can cause embryo-fetal toxicity, including fetal death. Use in pJIA is contraindicated
in pregnancy. Consider the benefits and risks of XATMEP and risks to the fetus when prescribing
XATMEP to a pregnant patient with a neoplastic disease. Advise females and males of reproductive
potential to use effective contraception during and after treatment with XATMEP [see Contraindications
(4), Warnings and Precautions (5.9), Use in Specific Populations (8.1, 8.3)].

INDICATIONS

XATMEP is a folate analog metabolic inhibitor indicated for the:

treatment of pediatric patients with acute lymphoblastic leukemia (ALL) as part of a multi-phase, combination chemotherapy maintenance regimen.

management of pediatric patients with active polyarticular juvenile idiopathic arthritis (pJIA) who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose non-steroidal anti-inflammatory agents (NSAIDs).

ADDITIONAL IMPORTANT SAFETY INFORMATION

Contraindications:

Xatmep is contraindicated in pregnant patients with non-malignant disease and in patients with severe
hypersensitivity to methotrexate.

Secondary malignancies can occur at all dose levels. Lymphoproliferative disease has been reported with
low-dose oral methotrexate which regressed when methotrexate is withdrawn.

Methotrexate can cause embryo-fetal toxicity and fetal death when administered during pregnancy. Consider the
risks and benefits of Xatmep and risks to the fetus when prescribing to a pregnant patient with a neoplastic
disease. Effective contraception should be practiced by patients of reproductive potential while receiving Xatmep
therapy, and for 3 and 6 months afterwards for males and females, respectively. Xatmep is contraindicated in
non-neoplastic disease.

Effects on reproduction: Methotrexate can cause impairment of fertility, oligospermia, and menstrual dysfunction.
It is unknown if the infertility is reversible in affected patients.

Pulmonary function tests may be useful if methotrexate-induced lung disease is suspected, especially
if baseline measurements are available.

Risk of improper dosing: Once-weekly dosing is appropriate. Fatal toxicity has been reported with daily dosing.
An accurate milliliter measuring device should be used. Inform patients that a household teaspoon is not an
accurate measuring device and could lead to overdosage.

Other frequently reported reactions are malaise, fatigue, chills and fever, dizziness, and decreased resistance
to infection.

The approximate incidences of adverse reactions reported in pediatric patients with JIA treated with oral, weekly
doses of methotrexate (5 to 20 mg/m2/week or 0.1 to 0.65 mg/kg/week) were as follows (virtually all patients
were receiving concomitant nonsteroidal anti-inflammatory drugs, and some also were taking low doses of
corticosteroids): elevated liver function tests, 14%; gastrointestinal reactions (e.g., nausea, vomiting, diarrhea),
11%; stomatitis, 2%; leukopenia, 2%; headache, 1.2%; alopecia, 0.5%; dizziness, 0.2%; and rash, 0.2%. Although
there is experience with dosing up to 30 mg/m2/week in JIA, the published data for doses above 20 mg/m2/week
are too limited to provide reliable estimates of adverse reaction rates.

Drug Interactions:

Penicillins may reduce the clearance of methotrexate; increased serum concentrations of methotrexate
with concomitant hematologic and gastrointestinal toxicity have been observed with methotrexate. Monitor
patients accordingly.

Denver, September 8, 2014—Silvergate Pharmaceuticals, Inc. (www.Silvergatepharma.com), focused on the development and commercialization of innovative and safe medicines for children, today announced that the United States Food and Drug Administration (FDA) approved Epaned® (Enalapril Maleate Powder for Oral Solution) for the treatment of symptomatic heart failure and the treatment of asymptomatic left ventricular dysfunction (to decrease the rate of development of overt heart failure and to reduce hospitalization for heart failure). These indications are in addition to the prior approval for hypertension (high blood pressure) in patients older than 1 month.1Read full article “FDA Approves 2 New Indications for Epaned®, the First and Only Enalapril Powder for Oral Solution”